This proposal is for the investigation of the kinetics of transcorneal flux and intraocular fate of pilocarpine. Methodology and mechanism of flux enhancement is of special interest. Central to this series of studies is the use of a transport chamber to test drug transport across the rabbit cornea in the closed system under simulated physiological conditions. Previous work with this chamber has shown that pilocarpine flux efficiency is inversely related both to loading dose and retention ("depot") of drug within the cornea. The "depot" effect and transcorneal flux inhibition are significantly reduced by the mediation of various hydrogel polymer vehicles. These preliminary studies suggest that topically administered drugs of low lipid solubility are transported into the internal eye mainly by slow diffusion, but also by another mechanism which is more efficient than that governing high dose flux, which is mobilized by hydrogen mediated delivery, and probably both saturable and inhibited by high drug doses. Data supporting these impressions require confirmation and expansion. The proposed investigations are designed to determine the anatomical site and kinetics of flux inhibition, the therapeutic significance of intracorneal pilocarpine retention as a "reservoir" and the relation of retention to the mechanism of hydrogel mediated flux enhancement. Vehicle mediated transcorneal penetration kinetics of carbachol, an effective but poorly penetrating cholinergic, will be investigated to test if flux characteristics of pilocarpine may be applicable to other drugs, and as a possible competitive inhibitor for carrier mediation of low dose pilocarpine flux. The potential of carbachol flux enhancement by hydrogel polymers will be evaluated at the same time. Various polymer solutions will be evaluated to determine if flux enhancement capability is related to structure or viscosity.